High rates of relapse to drug use after long periods of abstinence characterize the behavior of experienced users of heroin, cocaine and other drugs of abuse. Past research indicates that the most potent event for provoking relapse to drug-taking is re-exposure to the previously used drug. Another factor thought to be important in relapse to drug- taking in humans is exposure to stress. Studies conducted recently in this laboratory have shown that brief exposure to intermittent footshock potently reinstates heroin-seeking behavior in rats following a prolonged drug-free period. At present, the neurobiological mechanisms involved in the effect of stress on relapse are not known. The purpose of the proposed research is to characterize the behavioral and neurochemical bases of stress-induce relapse, and to compare these to those underlying relapse induced by re- exposure to heroin and cocaine. In order to achieve this end, behavioral, pharmacological, and neurochemical methods will be used. The primary behavioral method to be used is the reinstatement procedure, a reliable animal model of relapse to drug use. Pharmacological methods will be used to examine the effect on stress- and drug-induced relapse of systemic and intracranial injections of drugs (agonists and antagonists of neurotransmitters implicated in drug reinforcement and dependence, and the stress response). Studies using in vivo microdialysis in the behaving animal will be done to examine changes in neurotransmitters release in specific brain areas in response to those events that provoke relapse, and to determine how such changes might be altered by long-term exposure to drugs of abuse. It is hoped that findings from the proposed research will contribute to a better understanding of relapse to drug use provoked by exposure to stress and drugs, and point to potential treatments to decrease relapse during periods of abstinence.